Local Pharmacologic Therapy for Pyoderma Gangrenosum

Methods

Two investigators conducted a search of English language publications using MEDLINE, PubMed, EMBASE, Cumulative Index to Nursing and Allied Health Literature, and EBSCO databases from inception until November 2017. The search used a combination of key words and controlled vocabulary for the concepts pyoderma gangrenosum, topical treatments, injectabletreatments, corticosteroids, and immunomodulatory, which were adapted to each database. Citations of retrieved articles were searched to extract publications not identified in the database search.

Table. Summary of local treatments for PG
DRUG	MECHANISM OF ACTION	VEHICLE	DOSAGE AND FREQUENCY	MONO-THERAPY	ADJUVANT	APP	PRODUCT OUTCOMES^a
Clobetasol propionate,^9,10 methylprednisolone,¹¹ triamcinolone diacetate,^6,7 Dexamethasone²³	Decreases production of proinflammatory molecules	Clobetasol propionate/methylprednisolone: cream, ointment; triamcinolone, dexamethasone: solution	Clobetasol propionate: 0.05%, BID; betamethasone: NS; methylprednisolone: 400g silvadene/4g methylprednisolone mixture, BID; triamcinolone: 6mg/mL, every 2 d for 2 wk, 40mg/mL (1-time dose); dexamethasone: 20mg, daily	Yes	Yes, systemic corticosteroids, dapsone	Topical to wound bed or intralesional (triamcinolone)	Clobetasol propionate: 1 pt healed in 9 wk; 49 pt healed in avg of 18 wk. Intralesional triamcinolone: 1 pt healed in 3 wk. Intralesional dexamethasone: 1 pt healed in 17 mos
Methotrexate^24,25	Increases synthesis of adenosine^b	Solution	25mg once weekly for 7 wk	No	Yes, systemic corticosteroids	Intralesional	Intralesional methotrexate: 1 pt had 90% improvement at 7 wk
Cyclosporine,^13,14 tacrolimus,^15–19 pimecrolimus^20–22	Impairs the proliferation and function of T lymphocytes and reduces production of inflammatory mediators	Cyclosporine: gel, solution; tacrolimus/pimecrolimus: ointment, cream, solution	Cyclosporine gel, daily. Cyclosporine solution: 250mg solution in 5mL water, daily; tacrolimus 0.03% and 0.1%, BID; tacrolimus 0.5% solution, daily, pimecrolimus 1% cream, BID	Yes	Yes, systemic corticosteroids	Topical to wound bed	Tacrolimus: 5 pt healed in avg 5 wk; 10 pt healed in avg 23 wk; 1 pt healed in 12 wk. Cyclosporine: 1 pt healed in 3 wk. Pimecrolimus: 1 pt healed in 12 wk
Cromolyn Sodium^27–30	Prevents mast cell degranulation	Solution	Cromolyn sodium 1%–4%, daily or BID	No	Yes, systemic corticosteroids	Topical to wound bed	5 pt healed in 5–8 wk range; 1 pt healed in 16 d; 2 pt nearly healed in 10–18 d range
Benzoyl Peroxide³²	Increases oxygen tension in tissues; stimulates epithelial growth	Solution	BPO 20%, BID	NS	NS	Topical to wound bed	1 pt achieved near-complete healing at 4 wk
Aminosalicylic Acid³³	Inhibits production of prostaglandins and leukotrienes; inhibits leukocyte toxicity and motility, preventing tissue destruction	Cream	5-ASA 10%, daily	No	Yes, systemic corticosteroids	Topical to wound bed	1 pt healed at 5 wk
Mustard^41,42	Cytotoxic agent	Solution	Nitrogen mustard 20% solution, daily	Yes	No	Topical to wound bed	1 pt healed at 12 wk
Phenytoin^34,35	Stimulates fibroblast proliferation, enhances formation of granulation tissue, decreases collagenaseactivity, decreases bacterial wound contamination, and decreases wound exudate	Solution	Phenytoin 2% solution, daily	No	Yes, systemic corticosteroids	Topical to wound bed	4 pt healed at 4 wk, 2 pt had significant improvement at 4 wk
Nicotine³⁶	Binds to non-cholinergic nicotine receptors on neutrophils and impede neutrophil ability to product superoxide	Cream	Nicotine 0.5%, daily	No	Yes, systemic corticosteroids	Topical to wound bed	2 pt healed in 4–8 wk range
Becaplermin³⁷	Promotes chemotactic recruitment and proliferation of cells involved in wound repair	Gel	Becaplermin 0.01%, daily	No	Yes, systemic corticosteroids	Topical to ulcer border	1 pt healed in 9 wk
Timolol³⁹	Beta2-antagonist can stimulate keratinocyte migration	Gel	Timolol maleate 0.5%, daily	No	Yes, topical collagenase	Topical to ulcer border	1 pt healed in 16 wk
Cannabis^43,44	Binds to cannabinoid receptors to provide pain relief	Oil	THC 2.5mg–5mg plus CBD 6mg, daily	No	Yes, systemic corticosteroids	Topical to wound bed	Pain relief and decreased utilization of opiate and non-steroidal pain medications.

Table. Summary of local treatments for PG

DRUG

MECHANISM OF ACTION

VEHICLE

DOSAGE AND FREQUENCY

MONO-THERAPY

ADJUVANT

APP

PRODUCT OUTCOMES^a

Clobetasol propionate,^9,10 methylprednisolone,¹¹ triamcinolone diacetate,^6,7 Dexamethasone²³

Decreases production of proinflammatory molecules

Clobetasol propionate/methylprednisolone: cream, ointment; triamcinolone, dexamethasone: solution

Clobetasol propionate: 0.05%, BID; betamethasone: NS; methylprednisolone: 400g silvadene/4g methylprednisolone mixture, BID; triamcinolone: 6mg/mL, every 2 d for 2 wk, 40mg/mL (1-time dose); dexamethasone: 20mg, daily

Yes

Yes, systemic corticosteroids, dapsone

Topical to wound bed or intralesional (triamcinolone)

Clobetasol propionate: 1 pt healed in 9 wk; 49 pt healed in avg of 18 wk. Intralesional triamcinolone: 1 pt healed in 3 wk. Intralesional dexamethasone: 1 pt healed in 17 mos

Methotrexate^24,25

Increases synthesis of adenosine^b

Solution

25mg once weekly for 7 wk

Yes, systemic corticosteroids

Intralesional

Intralesional methotrexate: 1 pt had 90% improvement at 7 wk

Cyclosporine,^13,14 tacrolimus,^15–19 pimecrolimus^20–22

Impairs the proliferation and function of T lymphocytes and reduces production of inflammatory mediators

Cyclosporine: gel, solution; tacrolimus/pimecrolimus: ointment, cream, solution

Cyclosporine gel, daily. Cyclosporine solution: 250mg solution in 5mL water, daily; tacrolimus 0.03% and 0.1%, BID; tacrolimus 0.5% solution, daily, pimecrolimus 1% cream, BID

Yes

Yes, systemic corticosteroids

Topical to wound bed

Tacrolimus: 5 pt healed in avg 5 wk; 10 pt healed in avg 23 wk; 1 pt healed in 12 wk. Cyclosporine: 1 pt healed in 3 wk. Pimecrolimus: 1 pt healed in 12 wk

Cromolyn Sodium^27–30

Prevents mast cell degranulation

Solution

Cromolyn sodium 1%–4%, daily or BID

Yes, systemic corticosteroids

Topical to wound bed

5 pt healed in 5–8 wk range; 1 pt healed in 16 d; 2 pt nearly healed in 10–18 d range

Benzoyl Peroxide³²

Increases oxygen tension in tissues; stimulates epithelial growth

Solution

BPO 20%, BID

Topical to wound bed

1 pt achieved near-complete healing at 4 wk

Aminosalicylic Acid³³

Inhibits production of prostaglandins and leukotrienes; inhibits leukocyte toxicity and motility, preventing tissue destruction

Cream

5-ASA 10%, daily

Yes, systemic corticosteroids

Topical to wound bed

1 pt healed at 5 wk

Mustard^41,42

Cytotoxic agent

Solution

Nitrogen mustard 20% solution, daily

Yes

Topical to wound bed

1 pt healed at 12 wk

Phenytoin^34,35

Stimulates fibroblast proliferation, enhances formation of granulation tissue, decreases collagenaseactivity, decreases bacterial wound contamination, and decreases wound exudate

Solution

Phenytoin 2% solution, daily

Yes, systemic corticosteroids

Topical to wound bed

4 pt healed at 4 wk, 2 pt had significant improvement at 4 wk

Nicotine³⁶

Binds to non-cholinergic nicotine receptors on neutrophils and impede neutrophil ability to product superoxide

Cream

Nicotine 0.5%, daily

Yes, systemic corticosteroids

Topical to wound bed

2 pt healed in 4–8 wk range

Becaplermin³⁷

Promotes chemotactic recruitment and proliferation of cells involved in wound repair

Gel

Becaplermin 0.01%, daily

Yes, systemic corticosteroids

Topical to ulcer border

1 pt healed in 9 wk

Timolol³⁹

Beta2-antagonist can stimulate keratinocyte migration

Gel

Timolol maleate 0.5%, daily

Yes, topical collagenase

Topical to ulcer border

1 pt healed in 16 wk

Cannabis^43,44

Binds to cannabinoid receptors to provide pain relief

Oil

THC 2.5mg–5mg plus CBD 6mg, daily

Yes, systemic corticosteroids

Topical to wound bed

Pain relief and decreased utilization of opiate and non-steroidal pain medications.

A Comprehensive Review of Local Pharmacologic Therapy for Pyoderma Gangrenosum

Methods

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A Comprehensive Review of Local Pharmacologic Therapy for Pyoderma Gangrenosum

Methods

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